Combined landscape of single-nucleotide variants and copy-number alterations in clonal hematopoiesis

Abstract

AbstractImplicated in the development of hematological malignancies (HM) and cardiovascular mortality, clonal hematopoiesis (CH) in apparently healthy individuals has been investigated by detecting either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here by combining targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in a general population of 11,234 individuals, including 672 with subsequent HM development. Both CH-related lesions significantly co-occurred, which combined, affected blood count, hypertension, and the mortality from HM and cardiovascular diseases depending on the total number of both lesions, highlighting the importance of detecting both lesions in the evaluation of CH.